Arch. Pharm. Chem. Life Sci. 2010, 343, 274–281
New 2,3-Dihydroquinazolin-4(1H)-ones
279
5.80 (m, 1H, C5-pyrazole H), 6.782–8.269 (m, 17H, ArH) ppm; MS
m/z (rel. int.): 503 [M+] (100), 358 (56.1), 281 (12.2), 251 (12.2), 236
(39), 57 (22). Anal. calcd. for C30H25N5O3 (503.55): C, 71.56; H, 5.00;
N, 13.91. Found: C, 71.53; H, 4.72; N, 13.64.
3-[4-(3-Phenylacryloyl)phenyl]-1-ethyl-2,3-
dihydroquinazolin-4(1H)-one 4h
Yield: 41%; m.p.: 167–1688C; crystallized from dioxane; IR m:
3052 (CH, aromatic), 2967 (CH, aliphatic), 1656, 1598 (CO), 1500
(C=C) cm–1; 1H-NMR (300 MHz) d: 1.129–1.153 (t, 3H, CH3), 3.515–
3.567 (q, 2H, CH2CH3), 5.078 (s, 2H, CH2N), 6.893–7.003 (m, 2H,
acryloyl H), 7.451–8.235 (m, 13H, ArH) ppm; MS m/z (rel. inten-
sity): 382 [M+] (22.9), 381 (36.2), 119 (72.4), 77 (100). Anal. calcd.
for C25H22N2O2 (382.45): C, 78.51; H, 5.80; N, 7.32. Found: C, 78.75;
H, 5.61; N, 7.50.
2-[1-(4-(1-Methyl-4-oxo-1,2-dihydroquinazolin-
3(4H)yl)phenyl)ethylidene]hydrazinecarbothioamide 6
A mixture of compound 3a (0.01 mol) and thiosemicarbazide
(0.01 mol) in ethanol (20 mL) containing ten drops of glacial ace-
tic acid was heated under reflux for 2 h. The separated solid was
filtered, washed, dried, and recrystallized from dioxane/DMF
mixture (5:1).
General procedure for preparation of compounds 5a–d
To a suspension of compound 4a or 4b (0.001 mol) in ethanol,
hydrazine hydrate (99%, 0.1 mL, 0.002 mol) or phenylhydrazine
(0.001 mol) was added. The reaction mixture was refluxed for 12
h and then concentrated. After cooling, the obtained crystalline
product was filtered and recrystallized from the proper solvent.
Yield: 84%; m.p.: 2408C; IR m: 3407, 3270, 3198 (NH2, NH), 3154
(CH, aromatic), 2965 (CH, aliphatic), 1659 (CO), 1593 (C=N), 1495
1
(C=C) cm–1; H-NMR (200 MHz) d: 2.34 (s, 3H, CH3), 2.955 (s, 3H,
NCH3), 4.938 (s, 2H, CH2N), 6.904–8.034 (m, 8H, ArH), 8.34 (s, 1H,
NH exch.), 10.216 (br s, 2H, NH2, exch.) ppm; MS m/z (rel. int.):
355 [M+ + 2] (12.8), 353 [M+] (19.1), 279 (100), 237 (14.9), 194 (19.1),
161 (29.8), 108 (17), 55 (29.8). Anal. calcd. for C18H19N5O5 (353.44):
C, 61.17; H, 5.42; N, 19.81. Found: C, 61.01; H, 5.61; N, 19.51.
3-[4-(5-(4-Methoxyphenyl)-4, 5-dihydro-1H-pyrazol-3-
yl)phenyl]-1-methyl-2,3-dihydroquinazolin-4(1H)-one 5a
Yield: 87%; m.p.: 1758C; crystallized from ethanol; IR m: 3330
(NH), 3045 (CH, aromatic), 2956 (CH, aliphatic), 1660 (CO), 1598
(C=N), 1508 (C=C) cm–1; 1H-NMR (300 MHz) d: 2.882–2.888 (m, 1H,
C4-pyrazole H), 2.917 (s, 3H, NCH3), 3.383 (m, 1H, C4-pyrazole H),
3.739 (s, 3H, OCH3), 4.781 (m, 1H, C5-pyrazole H), 4.832 (s, 2H,
CH2N), 6.887–7.852 (m, 12H, ArH), 10.20 (s, 1H, NH, exch.) ppm;
MS m/z (rel. int.): 414 [M+ + 2] (4.7), 413 [M+ + 1] (15), 412 [M+] (57.5),
279 (15), 206 (10.2),145 (19.7), 104 (100). Anal. calcd. for
C25H24N4O2 (412.48): C, 72.80; H, 5.86; N, 13.58. Found: C, 72.36;
H, 5.95; N, 13.66.
General procedure for preparation of compounds 7a, b
A suspension of compound 6 (0.001 mol) and the appropriate
phenacyl bromide (0.0015 mol) in ethanol (20 mL) was heated
under reflux for 3 h. Then, anhydrous sodium acetate (0.0015
mol) was added and the reaction mixture was heated again
under reflux for 12 h. It was cooled and poured into cold water
(100 mL). The separated solid was filtered, dried, and recrystal-
lized from a suitable solvent.
3-[4-(1-(2-(4-((4-Chlorophenyl)thiazol-2-yl)hydrazono)-
ethyl)phenyl]-1-methyl-2,3-dihydroquinazolin-4(1H)-one
3-[4-(5-(4-Methoxyphenyl)-1-phenyl-4,5-dihydro-1H-
pyrazol-3-yl)phenyl]-1-methyl-2,3-dihydroquinazolin-
4(1H)-one 5b
Yield: 42%; m.p.: 198–2008C; crystallized from dioxane; IR m:
3039 (CH, aromatic), 2997 (CH, aliphatic), 1652 (CO), 1596 (C=N),
1498 (C=C) cm–1; 1H-NMR (200 MHz) d: 2.947 (s, 3H, NCH3), 3.047–
3.165 (dd, 1H, C4 pyrazole H), 3.716 (s, 3H, OCH3), 3.829–3.974
(dd, 1H, C4-pyrazole), 4.927 (s, 2H, CH2N), 5.406–5.496 (dd, 1H, C5-
pyrazole H), 6.887–7.814 (m, 17H, ArH) ppm. Anal. calcd. for
C31H28N4O2 (488.58): C, 76.21; H, 5.78; N, 11.47. Found: C, 76.14;
H, 5.54; N, 11.47.
7a
Yield: 66%; m.p.: 283–2848C; crystallized from DMF/H2O (1:1); IR
m: 3216 (NH), 3061 (CH, aromatic), 2986 (CH, aliphatic), 1648
(CO), 1559 (C=N), 1498 (C=C) cm–1; 1H-NMR (200 MHz) d: 2.350 (s,
3H, CH3), 2.942 (s, 3H, NCH3), 4.927 (s, 2H, CH2N), 6.889–7.927 (m,
13H, ArH + C5-thiazole H), 11.310 (s, 1H, NH, exch.) ppm; MS m/z
(rel. int.): 489 [M+ + 2] (23.8), 488 [M+ + 1] (30.1), 487 [M+] (59.1), 278
(96.4), 210 (42.7), 168 (35), 105 (100). Anal. calcd. for C26H22ClN5OS
(488.00): C, 63.99; H, 4.54; N, 14.35. Found: C, 64.01; H, 4.26; N,
14.04.
3-[4-(5-(4-Nitrophenyl)-4,5-dihydro-1H-pyrazol-3-
3-[4-(1-(2-(4-Phenylthiazol-2-yl)hydrazono)ethyl)phenyl]-
yl)phenyl]-1-methyl-2,3-dihydroquinazolin-4(1H)-one 5c
Yield: 50%; m.p.: 308–3098C; crystallized from dioxane/DMF
(1:1); H-NMR (300 MHz) d: 2.759 (s, 1H, C4-pyrazole H), 2.983 (s,
3H, NCH3), 3.333–3.55 (m, 1H, C4-pyrazole H), 4.921 (br s, 1H, C5-
pyrazole H), 4.964 (s, 2H, CH2N), 6.917–8.107 (m, 12H, ArH), 13.57
(br s, 1H, NH, exch.) ppm. Anal. calcd. for C24H21N5O3 (427.46): C,
67.44; H, 4.95; N, 16.38. Found: C, 67.70; H, 4.56; N, 16.24.
1-methyl-2,3-dihydroquinazolin-4(1H)-one 7b
Yield: 71%; m.p.: 2058C; crystallized from dioxane/DMF (4:1); IR
m: 3213 (NH), 3062 (CH, aromatic), 2957 (CH, aliphatic), 1644
(CO), 1557 (C=N), 1503 (C=C) cm–1; 1H-NMR (200 MHz) d: 2.342 (s,
3H, CH3), 2.964 (s, 3H, NCH3), 4.94 (s, 2H, CH2N), 6.942–7.996 (m,
14H, ArH + C5-thiazole H), 11.310 (s, 1H, NH, exch.) ppm. Anal.
calcd. for C26H23N5OS (453.56): C, 68.85; H, 5.11; N, 15.44. Found:
C, 68.74; H, 4.97; N, 14.72.
1
3-[4-(5-(4-Nitrophenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-
3-yl)phenyl]-1-methyl-2,3-dihydroquinazolin-4(1H)-one
Pharmacology
5d
Animals
Yield: 41%; m.p.: 2338C; crystallized from dioxane; IR m: 2945
Male albino rats and male mice, weighing 150–200 g and 20–25
g each, respectively, were used. All experimental animals were
provided from the Faculty of Veterinary Medicine, Zagazig Uni-
versity, Egypt. All animals were held under standard laboratory
(CH, aliphatic), 1662 (CO), 1598 (C=N), 1497 (C=C) cm–1; H-NMR
(200 MHz) d: 2.970 (s, 3H, NCH3), 3.256–3.284 (m, 1H, C4-pyrazole
H), 3.951–4.103 (m, 1H, C4-pyrazole H), 4.942 (s, 2H, CH2N), 5.60–
1
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